Enzymes depending on the pterin molybdenum cofactor: sequence families, spectroscopic properties of molybdenum and possible cofactor-binding domains.
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Amino Acid Sequence↗
Biomedical subjects
D E Walters
Publications and source records attributed to D E Walters.
The ESHRE multicentre trial on the treatment of unexplained infertility: a preliminary report. European Society of Human Reproduction and Embryology.
Nineteen European fertility centres participated in a controlled randomized trial aimed at comparing the effectiveness of five methods for the treatment of unexplained infertility. Each centre was invited to employ two of the five treatments being investigated, and the treatment allocated to individual patients was then decided by randomization. The treatments were superovulation alone, and superovulation together with one of the following procedures: intra-uterine insemination (IUI), intra-peritoneal insemination (IPI), gamete intra-Fallopian transfer (GIFT), in-vitro fertilization (IVF). All the patients admitted to the study had experienced greater than 36 months infertility prior to the start of the trial, and only patients less than 38 years of age were included in the investigation. Further, the study was confined to patients with normal Fallopian tubes, and where there was evidence of spontaneous ovulation. Yet another prerequisite for inclusion in the study was that the male partner was 'normal' as regards fertility. Due to unavoidable practical difficulties, the experimental design eventually obtained was severely unbalanced. Nevertheless, objective statistical comparisons were possible among the five treatments, using non-orthogonal analyses of variance. By the completion of the trial 444 patients had been treated in a total of 649 cycles. There was some statistical evidence that the pregnancy rate obtained from superovulation alone was inferior to that obtained by using superovulation together with one of the methods of assisted conception.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Comment on the statistical evaluation of data.
This paper represents a plea for a more professional approach to the statistical evaluation of data contained in biological research papers. On the one hand more attention needs to be given to ensuring that statistically rigorous methods are employed; the use of sophisticated methods is now a possibility due to the wide availability of statistical computer packages. Examples are presented of some interesting applications of the multivariate techniques Cluster Analysis and Principal Component Analysis, the data being drawn from early research work into in-vitro fertilization.
Statistics as Topic↗
Ventilatory function and winter fresh fruit consumption in a random sample of British adults.
The relation between ventilatory function and the reported frequency of consumption of fresh fruit and fruit juice was studied among 1502 lifelong non-smokers and 1357 current smokers aged 18-69 with no history of chronic respiratory disease. Forced expiratory volume in one second (FEV1) was assessed by turbine spirometry. As winter fruit consumption was more widely dispersed than summer consumption and few subjects ate fruit more frequently in the winter, winter fruit consumption was taken as an indicator of habitual (year round) consumption. After adjustment for sex, age, height, cigarette consumption, region of residence, and household socioeconomic group, FEV1 was associated with winter fruit consumption. The mean adjusted FEV1 among those who never drank fresh fruit juice and ate fresh fruit less than once a week during the winter was 78 ml lower (95% confidence interval 24-132 ml) than the mean for the other subjects. A similar difference was found in all age-sex groups and among both current smokers and lifelong non-smokers. Antioxidant and other actions of vitamin C may protect against pulmonary emphysema, or reduce bronchoconstrictor responses to environmental pollutants.
Adolescent↗
Influence of host strain and helminth isolate on the first phase of the relationship between rats and Moniliformis moniliformis (Acanthocephala).
Eleven trials, involving 440 rats bred from 3 laboratory strains and worms from 4 isolates of Moniliformis moniliformis, were carried out with each rat receiving an oral dose of 15 cystacanths. The results showed that the infectivity of the cystacanths was not affected by their age (range 55-194 days) or by their density per cockroach during development (16.1-88.6 cystacanths per cockroach). The numbers of worms per rat recovered at 35 days postinfection (p.i.) were shown to be related to rat strain, with highly inbred strains (PVG and F344) being more supportive of numbers of worms than an outbred Wistar strain. There was no evidence to suggest that the sex of the rats had any influence on the numbers of worms recovered at 35 days p.i. Evidence was obtained to suggest that smaller (younger) rats are likely to support more worms on average than larger (older) rats. There was no evidence of any relationship between worm weight and numbers of worms present per rat on day 35 p.i. Generally, rat strain had little effect on the dry weight (growth) of male M. moniliformis, in contrast to observations made for female worms. The greatest range of worm weights was observed from the recent isolate of the worm (1982) as compared with the well established isolate (1956) and the rats that supported most worms differed from those that harbored the largest worms. Rat sex was not observed to be associated with worm weight. The frequency distributions of numbers of M. moniliformis per rat were not described readily by the negative binomial distribution.
Analysis of Variance↗
The D1 agonist SKF 38393 increases dopamine release in the developing rat striatum.
Changes in extracellular levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) following systemic injection of the D1 agonist SKF 38393, 10 mg/kg, the D1 antagonist SCH 23390, 0.5 mg/kg, or the mixed D1/ /D2 agonist apomorphine, 0.05 mg/kg, were monitored in the striatum of developing rats implanted with a dialysis probe. There was a significant age-related increase in DA in perfusates from adult and 35-36-day-old rats injected with SKF 38393 compared to 10-11- and 21-22-day-old rats. Also, SKF 38393 significantly decreased DOPAC and HVA in perfusates from 10-11-day-old rats when compared to the older aged rats. Pretreatment with SCH 23390 completely blocked the SKF 38393-induced increase in DA but not the SKF 38393-induced decrease in DOPAC and HVA. In contrast, there were no significant differences between ages in the response to DA to SCH 23390. However, SCH 23390 did produce a small, but significant, decrease in DOPAC and HVA at 10-11 days of age compared to the other ages. Forty minutes after injecting apomorphine, DA levels were decreased by 45% and remained near this level for the duration of the experiment. These results indicate that stimulation of DA D1, receptors can increase striatal DA release and that this ability is acquired between 21 and 35 days of age. This finding is consistent with the idea of opposing roles for DA D1 and D2 receptor subtypes.
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
Loss of striatal angiotensin-converting enzyme following intrastriatal AF64A is not related to destruction of cholinergic interneurons.
The potent angiotensin-converting enzyme (ACE) inhibitor 351A was radioiodinated (125I-351A) and used to quantitate ACE in the striatum of rats treated with the cholinergic neurotoxin AF64A. Unilateral administration of 4 nmol of AF64A into the striatum, which caused a 42% reduction in striatal choline acetyltransferase (ChAT) activity, reduced binding of 125I-351A in the lesioned striatum by 37% relative to the untreated striatum. The AF64A treatment also reduced the dopamine (DA) concentration by 59% in the lesioned striatum, but did not significantly reduce the serotonin (5-HT) concentration. Despite the reductions in ACE and these neurochemical markers, there was no significant correlation between the extent of reduction of the specific neurochemical markers and ACE. These results suggest that the AF64A treatment caused non-specific damage to striatal non-cholinergic neurons as well as destroying cholinergic neurons, and that ACE is contained in non-cholinergic neurons.
Animals↗
Development of haloperidol-induced dopamine release in the rat striatum using intracerebral dialysis.
Haloperidol-induced dopamine (DA) release and metabolism were studied in the rat striatum at 10-11, 21-22, and 35-36 days of age using intracerebral dialysis and HPLC with electrochemical detection. There was an age-related increase in basal DA release and extracellular levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), with the greatest increases occurring between 10-11 and 21-22 days of age. Haloperidol (0.1 mg/kg, i.p.) significantly increased DA release at each age compared to control. Also, haloperidol produced a significantly greater increase in DA release at 10-11 days than at 21-22 or 35-36 days of age when expressed as percentage of predrug release. Haloperidol increased DA release over 60 min to 235%, 138%, and 158% above baseline at 10-11, 21-22, and 35-36 days of age, respectively, after which time the levels remained relatively constant. Haloperidol significantly increased extracellular DOPAC and HVA levels at each age compared to controls, but there were no significant differences in DOPAC or HVA levels between ages in response to haloperidol. The results indicate that, at 10 days of age, DA release in the striatum is physiologically functional and that the regulatory feedback control of DA release and metabolism in the striatum develops prior to 10 days of age.
3,4-Dihydroxyphenylacetic Acid↗
Monoamine depletion does not alter angiotensin II binding sites in the rat brain.
6-Hydroxydopamine (6-OHDA) or 5,7-dihydroxytryptamine (5,7-DHT) was administered in the lateral cerebral ventricles of rats. These respective treatments caused reductions in norepinephrine (NE) and 5-hydroxytryptamine (5-HT) levels in the hypothalamus-thalamus-septum-midbrain (HTSM; 62% and 44%) and brainstem (57% and 26%), respectively. Catecholamine depletion in 6-OHDA-treated rats resulted in a 55% decrease in the pressor response to ICV Ang II which was not associated with any significant change in the binding of 125I-sarcosine1, isoleucine8 Ang II to Ang II binding sites in the HTSM or brainstem. The radioligand binding was not significantly affected by the 5,7-DHT treatment. These results indicate that brain Ang II binding sites are not predominantly localized on NE- or 5-HT-containing nerve terminals. They do not, however, preclude the existence of a small proportion of Ang II binding sites on these neuronal populations.
5,7-Dihydroxytryptamine↗
Soil-transmitted helminth infections in school children from Cocle Province, Republic of Panama.
A survey was carried out to determine values for the prevalence and intensity of infection of intestinal helminths in children living in Cocle Province, Republic of Panama. The data set consisted of the results of microscopic examinations (modified Kato Katz technique) of stool samples collected in November 1987 from 661 children attending primary schools in 4 communities in the province. The overall prevalences of Ascaris lumbricoides, hookworm and Trichuris trichiura infections were found to be 18.2, 12.0 and 27.5% respectively. There were significant differences between the infection prevalence values for children attending the different schools, but not with respect to age or sex. Positive associations were detected between particular pairs of infections and these were most evident when Trichuris trichiura was involved. The data revealed evidence of a positive association between siblings at one school only for each helminth infection. There was extreme variation in the values for intensity of infection (20-126180 epg for A. lumbricoides). Highly significant, and unexplained, differences were observed in the intensity of A. lumbricoides infection by primary school; this finding did not apply to hookworm or T. trichiura. The analysis also revealed that children heavily infected with A. lumbricoides were also likely to be heavily infected with T. trichiura. Comparisons with the results of surveys carried out in Cocle Province in 1926 and 1974 indicate that these infections are declining in this region of Panama.
Analysis of Variance↗
On the utility of statistical modelling in reproductive studies.
The usefulness of mathematical modelling is discussed, with reference to a beta-binomial model which is used to describe both the implantation and birth statistics after assisted procreation. The relatively heavy computing effort required is emphasized, and contrasted with the rather simpler calculations associated with traditional statistical methods. The advantages of deriving a concise description of the data with a few important, and easily interpretable, parameters are also discussed. Numerical data provided by an IVF clinic are used to illustrate the mathematical procedures and to provide an assessment of the success of the modelling exercise.
Female↗
The factor structure of the General Health Questionnaire (GHQ-30). A reliability study on 6317 community residents.
An individual's responses to Goldberg's 30-item General Health Questionnaire are usually represented as a single score which provides a measure of the number of psychiatric symptoms reported. No account is taken of the nature of the symptoms. Factor analyses of the GHQ-30 were undertaken in ten randomly selected samples of 600 adults each, and also on 12 age-sex groupings covering the age range 18-98. The results indicate an impressive degree of consistency of the factor structure, and the identification of five distinct factors corresponding to anxiety, feelings of incompetence, depression, difficulty in coping, and social dysfunction.
Adaptation, Psychological↗
Neurotransmitters and lymphatic-vascular transfer of prostaglandin F2 alpha stimulate ovarian oxytocin output in sheep.
The mechanisms of lymphatic-vascular transfer across the ovarian vascular pedicle were studied in anaesthetized sheep 8-15 days after ovulation. [3H]Prostaglandin F2 alpha (PGF2 alpha), [14C]mannitol and [36Cl]Na were infused continuously into either a uterine lymphatic or a uterine vein and the kinetics of transfer into the adjacent utero-ovarian vein or ovarian plasma were studied. Transfer occurred according to the sequence [36Cl] greater than [14C] greater than [3H] indicating that PGF2 alpha is not transferred by rapid diffusion, as with [36Cl]Na, nor by a paracellular route, as with [14C]mannitol, but by a slower process probably involving facilitated diffusion. Transfer into the adjacent utero-ovarian vein or ovarian blood was greater when compounds were infused into a uterine lymphatic than into a uterine vein. Substantially more [3H]PGF2 alpha occurred in the adjacent corpus luteum than either of the other compounds after a lymphatic infusion. Intra-lymphatic infusion of PGF2 alpha stimulated the release of ovarian oxytocin but the effect was not confined to the adjacent ovary. Intravenous (jugular) infusion of PGF2 alpha failed to stimulate ovarian oxytocin secretion whereas close-arterial infusion into the ovaries was effective, and the possibility was investigated that any systemic effect of PGF2 alpha was mediated through neural mechanisms. Noradrenaline and acetylcholine were both effective in causing the release of ovarian oxytocin when infused close-arterially into the ovary. With infusions of acetylcholine, ovarian oxytocin secretion rate was increased over fivefold without any change in posterior pituitary release. Noradrenaline and acetylcholine produced a concomitant fall in ovarian blood flow, and neurotransmitter-induced ischaemia may have played a role in ovarian oxytocin release. The finding that PGF2 alpha infused into a uterine lymphatic stimulates ovarian secretion of oxytocin, and that the effect is bilateral whereas PGF2 alpha accumulation in ovarian tissue is unilateral, implies that its mechanism of action may not be solely directed at the luteal cell.
Acetylcholine↗
Perinatal exposure to cannabinoids alters neurochemical development in rat brain.
Adult female rats received daily oral doses of delta 9-tetrahydrocannabinol (delta 9-THC), delta 8-THC and cannabidiol (CBD) throughout gestation and lactation. The offspring were sacrificed at various ages and tissue samples of cerebral cortex and striatum were assayed for alpha 1-adrenergic and D2-dopaminergic receptors, respectively. In addition, tyrosine hydroxylase activity was determined in the striatum. The Kd for ligand binding to alpha 1 receptors in the cerebral cortex was significantly increased in 10-day-old offspring exposed to CBD. Significant increases in the Bmax of these receptors occurred at 20 days of age following perinatal exposure to delta 9-THC or delta 8-THC. Exposure to CBD increased the Kd of D2 receptors in the striatum of 10 and 20-day-old offspring compared to control. There were no significant treatment effects on the Bmax of D2 receptors in the striatum at any age. Tyrosine hydroxylase activity was significantly decreased only at 60 days of age in offspring exposed to delta 8-THC or CBD. These results differ from those previously reported with a crude marihuana extract, suggesting that changes in the development of brain catecholamine mechanisms resulting from perinatal exposure to marihuana extracts may be due to an additional constituent of the extract, interactions between specific cannabinoids or other unknown factors.
Aging↗
Potential antisecretory antidiarrheals. 1. Alpha 2-adrenergic aromatic aminoguanidine hydrazones.
Guanabenz, a centrally acting antihypertensive agent, has been shown to have intestinal antisecretory properties. A series of aromatic aminoguanidine hydrazones was made in an effort to separate the antisecretory and cardiovascular activities. Benzaldehyde, naphthaldehyde, and tetralone derivatives were synthesized. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and in the Ussing chamber using a rabbit ileum preparation. A number of compounds, including members of each structural class, were active upon subcutaneous administration in the rat. Active compounds were determined to be alpha 2-adrenergic agonists by yohimbine reversals of their Ussing chamber activities. The compound displaying the best separation of activities was the aminoguanidine hydrazone of 2,6-dimethyl-4-hydroxybenzaldehyde (20).
Adrenergic alpha-Agonists↗
Neuronal localization of specific angiotensin II binding sites in the rat inferior olivary nucleus.
Adult male Sprague-Dawley rats were treated with 3-acetylpyridine, a neurotoxin selective for the inferior olivary nucleus. Following treatment, the rats exhibited deficits in locomotor behavior indicative of destruction in the inferior olivary nucleus. The rats were sacrificed 3 weeks later, and the binding of 125I-sarcosine, isoleucine angiotensin II to brain homogenates and slide-mounted sections of brainstem was determined. Treatment with 3-acetylpyridine significantly decreased specific 125I-sarcosine, isoleucine angiotensin II binding in homogenates of posteroventral brainstem (containing the inferior olivary nucleus) by approximately 50%. Homogenates of dorsal brainstem and hypothalamus-thalamus-midbrain showed no significant changes in specific binding. Treatment with 3-acetylpyridine did not significantly alter the radioligand binding affinity which was determined in the hypothalamus-thalamus-midbrain. Autoradiographic analysis of 125I-sarcosine, isoleucine angiotensin II binding in the brainstem sections indicated that specific angiotensin II binding sites in the inferior olivary nucleus were virtually eliminated by the 3-acetylpyridine treatment. In addition, a comparatively small, but significant, decrease in specific 125I-sarcosine, isoleucine angiotensin II binding occurred in the solitary tract nucleus/dorsal vagal motor nucleus complex. These results indicate that specific angiotensin II binding sites in the inferior olivary nucleus occur exclusively on neuronal perikarya and/or dendrites.
1-Sarcosine-8-Isoleucine Angiotensin II↗
Measurement of angiotensin converting enzyme with mono 125I-351A.
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Angiotensin-Converting Enzyme Inhibitors↗
Identical twins and in vitro fertilization.
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Blastocyst↗